Oxidation of alcohols using dimethyl sulfoxide

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Scheme 12.3. Oxidation of Alcohols Using Dimethyl Sulfoxide... 

One potential activator for dimethyl sulfoxide that in practice turns out to be very poor, is phosgene. However, a related oxidation of alcohols using dimethyl sulfoxide does use phosgene for the preparation of a chloroformate (or carbonochloridate) such as (29). - This reacts with dimethyl sulfoxide to give, after spontaneous loss of carbon dioxide, an alkoxysulfonium salt (30) which upon treatment with tri-ethylamine fonns the carbonyl compound (Scheme 7). Relatively little use appears to have been made of this method. 

Although many oxidizing reagents remove the chromium tricarbonyl group, benzylic alcohols can be oxidized to benzaldehydes using dimethyl sulfoxide with acetic anhydride, trifluoroacetic anhydride, or sulfurtrioxide with minimal decomplexation. Asymmetric oxidation of aUcylthio-substituted complexes can be achieved using titanium tetraisopropoxide and an optically active tartrate ester (Scheme 108). Dimethyloxirane can also be used to oxidize sulfides to sulfoxides. 

NaHCOs, and methanesulfonic anhydride.Dimethyl sulfoxide in 48% HBr oxidizes benzylic alcohols the aryl aldehydes.Note that Swern oxidation of molecules having alcohol moieties, as well as a disulfide, leads to the ketone without oxidation of the sulfur. Sulfoxides other than DMSO can be used in conjunction with oxalyl chloride for the oxidation of alcohols,including fluorinated sulfoxides and a polymer-bound sulfoxide. ... 

Oxidations of alcohols using the dimethyl sulfoxide-oxalyl chloride combination are known as Swern oxidations after Daniel Swern of Temple University who developed the method. 

Dimethyl sulfoxide reacts with trifluoroacetic anhydride at low tempera ture to give a complex that is an efficient reagent for the oxidation of alcohols to carbonyl compounds [40 41] This reagent can be used to oxidize primary and secondary aliphatic alcohols, cycloalkyl alcohols, and allylic, homoallylic, ben-zylic, acetylenic, and steroidal alcohols (equation 19)... 

Similar reaction pathways have also been found for the oxidation of dimethyl sulfide to dimethyl sulfoxide and dimethyl sulfoxide to dimethyl sulfone by [Ru(bpy)2(py)(0)]2+ with respective rate constants of 17.1 and 0.13 M l s"1 in MeCN at 298 K (48). The complex [Ru(bpy)2 (py)(0)]2+ has also been used electrocatalytically for the oxidation of alcohols, aldehydes, alkenes, and aromatics (23, 49). The kinetics of oxidation of formic acid/formate ion by [Ru(bpy)2(py)(0)]2 +, with a large kinetic isotope effect [ HC02-/ADCo2- = 19 (25°C, /r = 1.0 M)], has been reported (50). A two-electron hydride transfer has been suggested for the oxidation of HC02 by [Ru(bpy)2(py)(0)]2+. A similar mechanism has also been suggested for the oxidation of alcohols (51) and aromatics (52) by [Ru(bpy)2(py)(0)]2+ and other related Ru(IV) oxo complexes (28,... 

Ube Industries LtdinYamaguchi, Japan, and Kyoto University investigated the Swern oxidation for pharmaceutical intermediates [57,58]. In this reaction, alcohols are oxidized to carbonyl compounds using dimethyl sulfoxide. The reaction variant using dimethyl sulfoxide activated by trifluoroacetic anhydride (shown below) has found industrial application, but is limited to low-temperature operation (—50 °C or below) to avoid decomposition of an intermediate. 

The Swern oxidation uses dimethyl sulfoxide (DMSO) as the oxidizing agent to convert alcohols to ketones and aldehydes. DMSO and oxalyl chloride are added to the alcohol at low temperature, followed by a hindered base such as triethylamine. The reactive species (CH3)2SC1, formed in the solution, is thought to act as the oxidant in the Swem oxidation. Secondary alcohols are oxidized to ketones, and primary alcohols are oxidized only as far as the aldehyde. The by-products of this reaction are all volatile and are easily separated from the organic products. 

The key to successfiilly using dimethyl sulfoxide as an oxidant for alcohols is to activate the sulfur atom prior to reaction with a nucleophilic alcohol function. This activation involves electrophilic attack upon the sulfinyl oxygen by a varied of electrophiles. The initial product formed when an alcohol does attack the activated dimethyl sulfoxi is known to be the sulfcmium salt (1 Scheme 1). 

Thionyl chloride appears to be siqrerior to trifluoroacetic anhydride as an activator of dimethyl sulfoxide during the oxidation of alcohols in terms of yields of carbonyl compounds, although it has not been as widely used. The active species in this process, leading to an alkoxysulfonium species, is probably the ion pair (26). 

Protection of aldoses at the non-anomeric positions makes it possible to use many of the common procedures in organic chemistry for oxidizing lactols as shown with mannofura-nose 1 and glucopyranose 3 (O Table 1). The reactions can be divided into three main categories oxidations mediated by activated dimethyl sulfoxide (DMSO), oxidations with chromi-um(VI) oxides, and oxidations catalyzed by ruthenium oxides. The DMSO-mediated oxidations of alcohols can be promoted by several activators [27]. With the partially protected aldoses the activation has mainly been achieved with acetic anhydride and oxalyl chloride. Competing /3-elimination does usually not occur unless the eliminating group is an ester, e. g., an acetate or a benzoate [27]. 

Roa-Gutierrez, F., Liu, H.-J. Use of silyl chlorides as dimethyl sulfoxide activators for the oxidation of alcohols. Bulletin of the Institute of... 

Pfitzner-Moffatt oxidation. Oxidation of alcohols to carbonyl derivatives with dimethyl sulfoxide and dicyclohexylcarbodiimide. The procedure is especially useful for the conversion of a primary alcohol to an aldehyde without further oxidation to the carboxylic acid. 

The Swern oxidation of alcohols to aldehydes is carried out with dimethyl sulfoxide. A polymeric version (5.53) used poly(hexylene sulfoxide), obtained by the oxidation of the corresponding sulfide with hydrogen peroxide to facilitate recovery and reuse, at the same time the bad smell of dimethyl sulfide was avoided. Quantitative yields were... 

Oxidations using dimethyl sulfoxide activated by various reagents began with discoveries by Komblum and co-workers that primary tosylates and certain a-bromo ketones could be converted into aldehydes and glycoxals, respectively, by treatment with dimethyl sulfoxide as the oxidising agent. This was followed by the discovery several years later by Pfitzner and Moffatt that alcohols could be oxidised to carbonyl compounds with dimethyl sulfoxide, dicyclohexylcarbodiimide (DCC) and phosphoric acid at room temperature.2 Eventually the method developed by Swern and co-workers, involving activation of dimethyl sulfoxide with oxalyl chloride, came to be the most synthetically useful and widely applied of these mild oxidation procedures.3-6... 

Because of the toxicity of chromium-based reagents, other methods for the oxidation of alcohols have been developed. One of the most widely employed methods, called the Swem oxidation, uses dimethyl sulfoxide [(CH3)2SO], oxalyl chloride [(COCl)2], and triethylamine. Since the reaction is not carried out in an... 

A very useful group of procedures for oxidation of alcohols to ketones have been developed that involve dimethyl sulfoxide (DMSO) and any one of a number of electrophilic molecules, particularly dicyclohexylcarbodiimide, acetic anhydride, and sulfur trioxide. The initial work involved the DMSO-dicyclo-hexylcarbodiimide system. The utility of the method has been greatest in the oxidation of molecules that are highly sensitive to more powerful oxidants and therefore cannot tolerate alternative methods. The mechanism of the oxidation involves formation of intermediate A by nucleophilic attack of DMSO on the carbodiimide, followed by reaction of this species with the alcohol. A major portion... 

Microflow systems serve as effective environments to perform various oxidation reactions using chemical reagents. The oxidation using dimethyl sulfoxide (DMSO), which is known as Moffatt-Swern type oxidation, is one of the most versatile and reliable methods for the oxidation of alcohols into carbonyl compounds in laboratory synthesis [1, 2]. However, it is well known that activation of DMSO leads to an inevitable side-reaction, Pummerer rearrangement, at temperatures above — 30°C (Scheme 7.1). Therefore, the reaction is usually carried out at low temperatures (—50 °C or below), where such a side-reaction is very slow [3, 4]. However, the requirement for such low temperatures causes severe limitations in the industrial use of this highly useful reaction. The use of microflow systems solves the problem. For example, the oxidation of cyclohexanol can be accomplished using a microflow... 

The oxidation of a secondary alcohol to a ketone or a primary alcohol to an aldehyde using dimethyl sulfoxide (DMSO) with oxalyl chloride at low temperature is called the Swern oxidation. Oxidation of an alkene with osmium tetroxide or potassium permanganate gives a cis-l,2-diol. 

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